Abstract The 21st century approach to discovering highly selective medicines and developing treatment strategies and therapeutic regimens for individual patients is undergoing revolutionary changes. Scientists in the field of drug metabolism are facing many new challenges in their quest to deliver the right drug at the precise dose to treat each patient's specific disease and achieve optimal results. The 46th Drug Metabolism Gordon Research Conference (GRC) will fill a major gap in addressing critical issues and novel approaches to achieve the goals of the precision medicine initiative that are of particular relevance to drug development scientists in the drug metabolism, transport, and pharmacokinetics/pharmacodynamics (DMPK) field. The aims of this GRC are to bring together scientists with expertise in diverse disciplines fundamental to DMPK and the precision medicine initiative to inform each other about technological advances and transformative approaches, to stimulate meaningful discussion, and to push the boundaries of science. The collegial nature of this GRC, and the unique format and setting, facilitate interactions and the development of new collaborations. Another aim is to foster the scientific development of young investigators, including postdoctoral fellows and graduate students, by providing a forum to expand their scientific breadth, interact with leaders in the field, and establish future collaborative relationships. One scientific session features presentations by young investigators selected from the submitted abstracts. The aims of this GRC will be accomplished by the internationally recognized keynote speaker, Dr. Allan Rettie, the eight scientific sessions facilitated by world-class discussion leaders and over 30 speakers, and the interactive nature of the meeting. Speakers in each session will present cutting-edge, unpublished data and innovative ideas on issues that are critical to the success of precision medicine. Topics range from new frontiers for DMPK scientists in pharmacogenomics; biomarker validation, qualification and use; identification of novel metabolic enzymes; a new generation of targeted covalent drugs with increased potency and longevity; drug transporter knowledge to enable precision medicine; in vitro and in silico models to improve predictions of drug efficacy and toxicity with a particular focus on kidney models; and dose individualization strategies to achieve precision medicine. Each speaker will stimulate audience discussion by including expert opinions about approaches to solve the most challenging and complex problems in achieving precision medicine relevant to that topic. With lectures in the mornings and evenings, the afternoons are available for informal discussions and recreation. Four, 2-hour poster sessions, with each poster presenter available for discussion during two sessions, will provide conferees ample opportunity to visit each poster with plenty of time for discussion, which is particularly ideal for young scientists. Participants in this timely GRC topic will discuss cutting-edge methods and the latest scientific findings, and debate the most reliable strategies and approaches to achieve more precise tailoring of medicines with optimal results for each patient.